NM_000382.3(ALDH3A2):c.471+1G>C AND Sjögren-Larsson syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 27, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001255500.1

Allele description [Variation Report for NM_000382.3(ALDH3A2):c.471+1G>C]

NM_000382.3(ALDH3A2):c.471+1G>C

Gene:

ALDH3A2:aldehyde dehydrogenase 3 family member A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_000382.3(ALDH3A2):c.471+1G>C

HGVS:

NC_000017.11:g.19652633G>C
NG_007095.2:g.8883G>C
NM_000382.3:c.471+1G>CMANE SELECT
NM_001031806.2:c.471+1G>C
NM_001369136.1:c.471+1G>C
NM_001369137.2:c.471+1G>C
NM_001369138.2:c.471+1G>C
NM_001369139.1:c.471+1G>C
NM_001369146.2:c.471+1G>C
NM_001369148.2:c.-218+1G>C
NC_000017.10:g.19555946G>C
NM_000382.2:c.471+1G>C

Molecular consequence:

NM_000382.3:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001031806.2:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369136.1:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369137.2:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369138.2:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369139.1:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369146.2:c.471+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369148.2:c.-218+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Sjögren-Larsson syndrome (SLS)
Synonyms:: FATTY ALCOHOL:NAD+ OXIDOREDUCTASE DEFICIENCY; Fatty aldehyde dehydrogenase deficiency; FADH deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010031; MedGen: C0037231; Orphanet: 816; OMIM: 270200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001431928	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 27, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001431928

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 27, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

RNA-based mutation screening in German families with Sjögren-Larsson syndrome.

Kraus C, Braun-Quentin C, Ballhausen WG, Pfeiffer RA.

Eur J Hum Genet. 2000 Apr;8(4):299-306.

PubMed [citation]

PMID:: 10854114

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001431928.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: ALDH3A2 c.471+1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. These predictions have been confirmed by functional study that demonstrated an in-frame deletion of exon 2 and 3 in a patient derived mRNA sample (Kraus_2000). The variant allele was found at a frequency of 4e-06 in 251416 control chromosomes (gnomAD). The variant, c.471+1G>C, has been reported in the literature in a compound heterozygous individual affected with Sjogren-Larsson Syndrome (Kraus_2000). This publication also evaluated the impact of the variant at the protein level, and demonstrated a significantly shortened protein product in a protein truncation test (Kraus_2000). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 10, 2023

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